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Database: UniProt
Entry: P39040
LinkDB: P39040
Original site: P39040 
ID   TYTR_CRIFA              Reviewed;         491 AA.
AC   P39040;
DT   01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1995, sequence version 1.
DT   26-NOV-2014, entry version 103.
DE   RecName: Full=Trypanothione reductase;
DE            Short=TR;
DE            EC=1.8.1.12;
DE   AltName: Full=N(1),N(8)-bis(glutathionyl)spermidine reductase;
GN   Name=TPR;
OS   Crithidia fasciculata.
OC   Eukaryota; Euglenozoa; Kinetoplastida; Trypanosomatidae;
OC   Leishmaniinae; Crithidia.
OX   NCBI_TaxID=5656;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=1453951; DOI=10.1111/j.1365-2958.1992.tb01766.x;
RA   Aboagye-Kwarteng T., Smith K., Fairlamb A.H.;
RT   "Molecular characterization of the trypanothione reductase gene from
RT   Crithidia fasciculata and Trypanosoma brucei: comparison with other
RT   flavoprotein disulphide oxidoreductases with respect to substrate
RT   specificity and catalytic mechanism.";
RL   Mol. Microbiol. 6:3089-3099(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX   PubMed=1542316; DOI=10.1016/0166-6851(92)90243-D;
RA   Field H., Cerami A., Henderson G.B.;
RT   "Cloning, sequencing, and demonstration of polymorphism in
RT   trypanothione reductase from Crithidia fasciculata.";
RL   Mol. Biochem. Parasitol. 50:47-56(1992).
RN   [3]
RP   PROTEIN SEQUENCE OF 39-62, AND CHARACTERIZATION.
RX   PubMed=3718941; DOI=10.1021/bi00360a007;
RA   Shames S.L., Fairlamb A.H., Cerami A., Walsh C.T.;
RT   "Purification and characterization of trypanothione reductase from
RT   Crithidia fasciculata, a newly discovered member of the family of
RT   disulfide-containing flavoprotein reductases.";
RL   Biochemistry 25:3519-3526(1986).
RN   [4]
RP   X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS), AND DISULFIDE BOND.
RX   PubMed=8477734; DOI=10.1111/j.1432-1033.1993.tb17734.x;
RA   Bailey S., Smith K., Fairlamb A.H., Hunter W.N.;
RT   "Substrate interactions between trypanothione reductase and N1-
RT   glutathionylspermidine disulphide at 0.28-nm resolution.";
RL   Eur. J. Biochem. 213:67-75(1993).
RN   [5]
RP   X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
RX   PubMed=1522596; DOI=10.1016/0022-2836(92)90701-K;
RA   Hunter W.N., Bailey S., Habash J., Harrop S.J., Helliwell J.R.,
RA   Aboagye-Kwarteng T., Smith K., Fairlamb A.H.;
RT   "Active site of trypanothione reductase. A target for rational drug
RT   design.";
RL   J. Mol. Biol. 227:322-333(1992).
RN   [6]
RP   X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
RX   PubMed=15299452; DOI=10.1107/S0907444993011898;
RA   Bailey S., Fairlamb A.H., Hunter W.N.;
RT   "Structure of trypanothione reductase from Crithidia fasciculata at
RT   2.6-A resolution; enzyme-NADP interactions at 2.8-A resolution.";
RL   Acta Crystallogr. D 50:139-154(1994).
RN   [7]
RP   X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS).
RX   PubMed=15299300; DOI=10.1107/S0907444994010772;
RA   Strickland C.L., Puchalski R., Savvides S.N., Karplus P.A.;
RT   "Overexpression of Crithidia fasciculata trypanothione reductase and
RT   crystallization using a novel geometry.";
RL   Acta Crystallogr. D 51:337-341(1995).
CC   -!- FUNCTION: Trypanothione is the parasite analog of glutathione;
CC       this enzyme is the equivalent of glutathione reductase.
CC   -!- CATALYTIC ACTIVITY: Trypanothione + NADP(+) = trypanothione
CC       disulfide + NADPH.
CC   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692;
CC       Note=Binds 1 FAD per subunit.;
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       pH dependence:
CC         Optimum pH is 7.5-8.0.;
CC   -!- SUBUNIT: Homodimer.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm.
CC   -!- PTM: The N-terminus is blocked.
CC   -!- MISCELLANEOUS: The active site is a redox-active disulfide bond.
CC   -!- SIMILARITY: Belongs to the class-I pyridine nucleotide-disulfide
CC       oxidoreductase family. {ECO:0000305}.
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DR   EMBL; Z12618; CAA78264.1; -; Genomic_DNA.
DR   EMBL; M73323; AAA30321.1; -; mRNA.
DR   EMBL; M73324; AAA30322.1; -; Genomic_DNA.
DR   EMBL; M73325; AAA30323.1; -; Genomic_DNA.
DR   PIR; S28002; S28002.
DR   PDB; 1FEA; X-ray; 2.20 A; A/B/C/D=2-491.
DR   PDB; 1FEB; X-ray; 2.00 A; A/B=2-491.
DR   PDB; 1FEC; X-ray; 1.70 A; A/B=2-491.
DR   PDB; 1TYP; X-ray; 2.80 A; A/B=1-487.
DR   PDB; 1TYT; X-ray; 2.60 A; A/B=1-487.
DR   PDB; 2TPR; X-ray; 2.40 A; A/B=2-491.
DR   PDBsum; 1FEA; -.
DR   PDBsum; 1FEB; -.
DR   PDBsum; 1FEC; -.
DR   PDBsum; 1TYP; -.
DR   PDBsum; 1TYT; -.
DR   PDBsum; 2TPR; -.
DR   ProteinModelPortal; P39040; -.
DR   SMR; P39040; 1-487.
DR   BindingDB; P39040; -.
DR   ChEMBL; CHEMBL5394; -.
DR   BioCyc; MetaCyc:MONOMER-13293; -.
DR   EvolutionaryTrace; P39040; -.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR   GO; GO:0015036; F:disulfide oxidoreductase activity; IEA:InterPro.
DR   GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR   GO; GO:0015042; F:trypanothione-disulfide reductase activity; IEA:UniProtKB-EC.
DR   GO; GO:0045454; P:cell redox homeostasis; IEA:InterPro.
DR   Gene3D; 3.30.390.30; -; 1.
DR   InterPro; IPR016156; FAD/NAD-linked_Rdtase_dimer.
DR   InterPro; IPR013027; FAD_pyr_nucl-diS_OxRdtase.
DR   InterPro; IPR004099; Pyr_nucl-diS_OxRdtase_dimer.
DR   InterPro; IPR023753; Pyr_nucl-diS_OxRdtase_FAD/NAD.
DR   InterPro; IPR012999; Pyr_OxRdtase_I_AS.
DR   InterPro; IPR001327; Pyr_OxRdtase_NAD-bd_dom.
DR   InterPro; IPR001864; Trypnth_redctse.
DR   Pfam; PF00070; Pyr_redox; 1.
DR   Pfam; PF07992; Pyr_redox_2; 1.
DR   Pfam; PF02852; Pyr_redox_dim; 1.
DR   PRINTS; PR00368; FADPNR.
DR   PRINTS; PR00470; TRYPANRDTASE.
DR   SUPFAM; SSF55424; SSF55424; 1.
DR   TIGRFAMs; TIGR01423; trypano_reduc; 1.
DR   PROSITE; PS00076; PYRIDINE_REDOX_1; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Cytoplasm; Direct protein sequencing; Disulfide bond;
KW   FAD; Flavoprotein; NADP; Oxidoreductase; Redox-active center.
FT   CHAIN         1    491       Trypanothione reductase.
FT                                /FTId=PRO_0000067988.
FT   NP_BIND      35     51       FAD.
FT   ACT_SITE    461    461       Proton acceptor.
FT   DISULFID     52     57       Redox-active.
FT                                {ECO:0000269|PubMed:8477734}.
FT   VARIANT     479    479       Q -> E.
FT   CONFLICT     16     16       G -> R (in Ref. 2; AAA30322/AAA30323).
FT                                {ECO:0000305}.
FT   CONFLICT     62     62       L -> Y (in Ref. 3; AA sequence).
FT                                {ECO:0000305}.
FT   CONFLICT    297    297       D -> E (in Ref. 2; AAA30321/AAA30322/
FT                                AAA30323). {ECO:0000305}.
FT   CONFLICT    454    454       F -> V (in Ref. 2; AAA30322/AAA30323).
FT                                {ECO:0000305}.
FT   STRAND        4     10       {ECO:0000244|PDB:1FEC}.
FT   HELIX        14     27       {ECO:0000244|PDB:1FEC}.
FT   STRAND       31     36       {ECO:0000244|PDB:1FEC}.
FT   STRAND       38     41       {ECO:0000244|PDB:1FEC}.
FT   TURN         42     44       {ECO:0000244|PDB:1FEC}.
FT   HELIX        51     55       {ECO:0000244|PDB:1FEC}.
FT   HELIX        57     75       {ECO:0000244|PDB:1FEC}.
FT   HELIX        76     79       {ECO:0000244|PDB:1FEC}.
FT   HELIX        85     87       {ECO:0000244|PDB:1FEC}.
FT   HELIX        92    115       {ECO:0000244|PDB:1FEC}.
FT   STRAND      120    131       {ECO:0000244|PDB:1FEC}.
FT   STRAND      134    142       {ECO:0000244|PDB:1FEC}.
FT   STRAND      147    158       {ECO:0000244|PDB:1FEC}.
FT   STRAND      162    164       {ECO:0000244|PDB:1FEC}.
FT   HELIX       172    174       {ECO:0000244|PDB:1FEC}.
FT   HELIX       178    181       {ECO:0000244|PDB:1FEC}.
FT   STRAND      189    194       {ECO:0000244|PDB:1FEC}.
FT   HELIX       198    210       {ECO:0000244|PDB:1FEC}.
FT   STRAND      216    227       {ECO:0000244|PDB:1FEC}.
FT   HELIX       232    244       {ECO:0000244|PDB:1FEC}.
FT   STRAND      247    251       {ECO:0000244|PDB:1FEC}.
FT   STRAND      255    260       {ECO:0000244|PDB:1FEC}.
FT   STRAND      266    270       {ECO:0000244|PDB:1FEC}.
FT   STRAND      275    283       {ECO:0000244|PDB:1FEC}.
FT   STRAND      287    290       {ECO:0000244|PDB:1FEC}.
FT   HELIX       292    294       {ECO:0000244|PDB:1FEA}.
FT   HELIX       296    299       {ECO:0000244|PDB:1FEC}.
FT   STRAND      322    324       {ECO:0000244|PDB:1FEC}.
FT   HELIX       326    329       {ECO:0000244|PDB:1FEC}.
FT   HELIX       335    350       {ECO:0000244|PDB:1FEC}.
FT   STRAND      364    366       {ECO:0000244|PDB:1FEC}.
FT   STRAND      368    370       {ECO:0000244|PDB:1TYT}.
FT   STRAND      372    376       {ECO:0000244|PDB:1FEC}.
FT   HELIX       379    385       {ECO:0000244|PDB:1FEC}.
FT   STRAND      387    396       {ECO:0000244|PDB:1FEC}.
FT   HELIX       399    404       {ECO:0000244|PDB:1FEC}.
FT   STRAND      411    418       {ECO:0000244|PDB:1FEC}.
FT   TURN        419    421       {ECO:0000244|PDB:1FEC}.
FT   STRAND      423    431       {ECO:0000244|PDB:1FEC}.
FT   HELIX       434    446       {ECO:0000244|PDB:1FEC}.
FT   HELIX       451    455       {ECO:0000244|PDB:1FEC}.
FT   HELIX       465    469       {ECO:0000244|PDB:1FEC}.
FT   STRAND      475    479       {ECO:0000244|PDB:1FEC}.
FT   STRAND      482    484       {ECO:0000244|PDB:1FEC}.
SQ   SEQUENCE   491 AA;  53229 MW;  EF749215A16F9187 CRC64;
     MSRAYDLVVI GAGSGGLEAG WNAASLHKKR VAVIDLQKHH GPPHYAALGG TCVNVGCVPK
     KLMVTGANYM DTIRESAGFG WELDRESVRP NWKALIAAKN KAVSGINDSY EGMFADTEGL
     TFHQGFGALQ DNHTVLVRES ADPNSAVLET LDTEYILLAT GSWPQHLGIE GDDLCITSNE
     AFYLDEAPKR ALCVGGGYIS IEFAGIFNAY KARGGQVDLA YRGDMILRGF DSELRKQLTE
     QLRANGINVR THENPAKVTK NADGTRHVVF ESGAEADYDV VMLAIGRVPR SQTLQLDKAG
     VEVAKNGAIK VDAYSKTNVD NIYAIGDVTD RVMLTPVAIN EGAAFVDTVF ANKPRATDHT
     KVACAVFSIP PMGVCGYVEE DAAKKYDQVA VYESSFTPLM HNISGSTYKK FMVRIVTNHA
     DGEVLGVHML GDSSPEIIQS VAICLKMGAK ISDFYNTIGV HPTSAEELCS MRTPAYFYQK
     GKRVEKIDSN L
//
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